1. Field of the Invention
The present invention relates to a method for producing optically active 1,2-diols, including optically active halogenohydrins, that can be used as chiral building blocks in the synthesis of optically active compounds used as pharmaceuticals, agrichemicals, physiologically active substances, and the like, and intermediates therefor. In particular, the present invention relates to a method for producing optically active 1,2-diols by means of assimilative optical resolution.
2. Description of the Related Art
Known biological methods for producing optically active 1,2-diols, including optically active halogenohydrins, using microorganisms are a method for producing an optically active 1,2-propanediol as disclosed in Japanese Unexamined Patent Publication No. 1994-30790 and a method for producing (S)-3-halogeno-1,2-propanediols as disclosed in Japanese Unexamined Patent Publication No. 1994-209781. In both methods, microorganisms as a resting cells belonging to the genus Pseudomonas are used.
The inventors have previously disclosed a method for producing an optically active 1,2-propanediol in Japanese Unexamined Patent Publication No. 2002-253295 and methods for producing optically active 3-chloro-1,2-propanediol in Japanese Unexamined Patent Publication Nos. 1991-191795, 2001-149090, and 1991-191794, in which a microorganism that proliferates by digesting an optically active compound as a carbon source is cultured in a culture medium containing a racemic mixture thereof as a sole carbon source, and the optically active compound that remains after culturing is recovered (assimilative optical resolution).
It is now known that, in the assimilative optical resolution described in the aforementioned patent publications, the ability of microorganisms to select optically active compounds is greatly affected by the quality and batch of the culture medium, especially the quality of water used in preparing the culture medium.
Generally, calcium is one of the important mineral elements in living bodies, and Ca2+ is known to be involved in controlling many life phenomena. There are industrially applicable techniques for microorganism culturing that take the Ca2+ concentration into consideration, for example, culturing for the production of unsaturated aliphatic acids (WO 98/029558), culturing for the decomposition of trichloroethylene (Japanese Unexamined Patent Publication No. 1999-46758), and culturing for the production of erythritol (Japanese Unexamined Patent Publication No. 1999-221092). However, there has been no report of the relationship between Ca2+ concentration and ability to select an optically active compound, i.e., the relationship between Ca2+ concentration and reaction rate and stereoselectivity (yield of chiral compound).